Kathleen M. Doody

Introduction of blastocyst culture and transfer for all patients in an in vitro fertilization program

OBJECTIVE To evaluate the nonselective application of extended embryo culture on the outcome of IVF. DESIGN Retrospective analysis. SETTING Private practice assisted reproductive technology center. PATIENT(S) Seven hundred ninety nonselected patients undergoing IVF with controlled ovarian stimulation. INTERVENTION(S) For day 3 ET, multicell embryos were cultured in human tubal fluid medium and 12% synthetic serum substitute. For day 5 ET, embryos were cultured for 48 hours in S1 medium and then for 48 hours in S2 medium. MAIN OUTCOME MEASURE(S) Implantation rate (determined by total no. of visualized gestational sacs), ongoing pregnancy rate, and number of embryos available for ET. RESULT(S) Respective day 3 and day 5 implantation rates for patients aged <35 years (29.5% and 38.9%), patients aged 35-39 years (20.7% and 28.2%), and all patients combined (23.3% and 32.4%) were statistically significantly different. Significantly more embryos were transferred on day 3 than on day 5 for patients aged <35 years (2.9 vs. 2.4), patients aged 35-39 years (3.1 vs. 2.6), and all patients combined (3.0 vs. 2.5). The difference in ongoing pregnancy rates per retrieval was statistically significant for day 3 compared with day 5 transfers for all patients combined (35.9% vs. 43.8%). Cancellation rates for transfer after retrieval increased significantly for day 3 compared with day 5 transfer (2.9% vs 6.7%). CONCLUSION(S) These results demonstrate the feasibility of using extended embryo culture in a nonselective manner for couples undergoing IVF. Overall, extended embryo culture was associated with a significant increase in pregnancy rates and implantation rates and a significant decrease in the number of embryos transferred. The rate of multiple implantation among patients aged <35 years warrants consideration of single blastocyst transfers for this group.

Use of recombinant human chorionic gonadotropin in ovulation induction

To review the use of hCG and to describe the clinical benefit of recombinant hCG (r-hCG) based on the published results of prospective, randomized studies. Review of published articles. Tertiary infertility care center.None.None. Oocyte number and quality, luteal phase progesterone, pregnancy and OHSS rate, and local tolerability. The published data consistently show that single doses of 250 microg r-hCG and 5,000 IU urinary (u)-hCG produce similar clinical outcomes when used in infertility treatment cycles for timed intercourse, IUI, and IVF in terms of the number of oocytes retrieved, number of mature oocytes harvested, and fertilization and pregnancy rates attained. Single doses of 10,000 IU u-hCG also gave results comparable to single doses of 250 microg r-hCG. P levels in the midluteal phase were significantly higher with the use of r-hCG compared with u-hCG, and local injection site adverse effects were significantly less frequent, demonstrating the higher purity of the recombinant product. A single 500-microg dose of r-hCG led to a higher rate of ovarian hyperstimulation syndrome compared with a 250-microg dose, with no significant improvement in pregnancy rates.A single dose of 250 microg r-hCG was at least as effective as single doses of 5,000 or 10,000 IU u-hCG but offered the advantages associated with use of a recombinant product: local injection site adverse effects were significantly less frequent with r-hCG than with u-hCG.

Abdominal myomectomy—a safe procedure in an ambulatory setting

OBJECTIVE To evaluate the efficacy and safety of minilaparotomy myomectomy in an ambulatory setting. DESIGN Retrospective, nonrandomized study. SETTING Center for Assisted Reproduction, Bedford, Texas. PATIENT(S) One hundred eighty-nine women desiring fertility with symptomatic uterine leiomyomata. INTERVENTION(S) Minilaparotomy myomectomy in an ambulatory setting. MAIN OUTCOME MEASURE(S) Operative time, blood loss, recovery time, postoperative analgesia, and complications. RESULT(S) The mean diameter of the largest leiomyoma was 4.4 cm (range, 1-14 cm). The mean number and weight of the leiomyomata was 4.9 (range, 1-35) and 109.8 gm (range, 1-1,165 g), respectively. The mean operative time was 73 minutes, and the mean blood loss was 96 mL. On average, patients required 3.5 hours of recovery time. In the recovery room, patients received a mean of 12 mg of morphine/37 mg of meperidine for pain control postoperatively before discharge home. Only one major complication, pulmonary edema related to extubation, occurred. CONCLUSION(S) This study demonstrates that minilaparotomy myomectomy, when performed using a systematic operative technique, can be accomplished in an outpatient setting with minimal blood loss, fast recovery time, and a low complication rate. Postoperatively, patients require minimal analgesia, which permits them to be discharged home the same day. Minilaparotomy myomectomy is a safe, cost-effective treatment of most symptomatic uterine leiomyomata in an ambulatory setting.

Precycle administration of GnRH antagonist and microdose HCG decreases clinical pregnancy rates without affecting embryo quality and blastulation

The outcome of a novel protocol utilizing precycle gonadotrophin-releasing hormone (GnRH) antagonist administration and LH activity support with microdose recombinant human chorionic gonadotrophin (HCG) was compared to GnRH agonist long protocol used in patients undergoing their first ICSI (n=707) or IVF (n=571) cycles, which had resulted in one or two blastocyst transfers. In GnRH antagonist cycles, cetrorelix acetate (3 mg) was administered s.c. 4 days before FSH stimulation and a repeat dose was given when the lead follicular diameter was 13-14 mm. LH support was provided by recombinant HCG (2.5 microg). Embryo progression and blastulation were evaluated using embryo progression indices and blastocyst quality scores. The tested protocol demonstrated reduced implantation and clinical pregnancy rates as compared with GnRH agonist long protocol, although the embryo progression and blastulation parameters and blastocyst quality were comparable among the groups. Logistic regression models further supported the significant negative impact of GnRH antagonist/microdose HCG protocol on clinical pregnancy rates in both ICSI and IVF patients. Assisted reproduction cycles with fresh blastocyst transfers utilizing precycle GnRH antagonist administration and microdose HCG support resulted in lower implantation and clinical pregnancy rates as compared with GnRH agonist cycles, although the embryo progression and blastulation parameters were comparable.

Repetitive oocyte donation does not decrease serum anti-Müllerian hormone levels

OBJECTIVE To determine if the anti-Müllerian hormone (AMH), a proposed marker of ovarian aging, decreases with repetitive oocyte donation. DESIGN Retrospective cohort. SETTING Academic. PATIENT(S) Thirty-six young women who underwent three to seven oocyte donation cycles. INTERVENTION(S) Assessor blind determination of AMH levels from serum samples collected during each treatment cycle. MAIN OUTCOME MEASURE(S) Cycle trends of serum AMH levels. RESULT(S) The AMH was the only predictor of oocyte yield in the first cycles. The AMH was negatively associated with donor age and follicle stimulating hormone (FSH) dose used. Serum AMH levels did not show any decrease per treatment cycle basis and per maximum number of oocyte donation cycles performed per woman. Whereas donors who underwent six cycles showed increasing AMH levels when controlled for studied covariates, the slopes of the multiple regression curves were not significantly different from donors who underwent three, four, and five cycles. Clinical outcome assessed by FSH dose/number of oocytes ratio did not show significant change over repetitive cycles. Intercycle variation of AMH in all patients over three cycles was found to be 12.5%, which was within the reported intermenstrual range. CONCLUSION(S) Serum AMH levels do not decrease over repetitive oocyte donation cycles, which may imply that accelerated ovarian aging may not occur in oocyte donors.

Successful Day 5 embryo transfer and pregnancies resulting after transport of embryos by air for biopsy and genetic analysis

Purpose: Case studies of four in vitro fertilization (IVF) cycles where embryo transport by commercial airline followed by biopsy and genetic analysis with subsequent culture to Day 5 and resulting ongoing pregnancy.Method: Retrospective clinical case study of 4 patients requiring preimplantation genetic diagnosis (PGD) testing. Normally fertilized embryos were transported in a battery-powered portable incubator by commercial airline following evaluation for fertilization under controlled conditions from the Center for Assisted Reproduction, Bedford, Texas to the Reproductive Genetic Institute, Chicago, Illinois. Following Day 3 embryo biopsy and genetic analysis, embryos were transported back to the Center for Assisted Reproduction for Day 5 embryo transfer.Results: Ongoing clinical pregnancy resulted for all patients receiving embryo transfer.Conclusion: These results demonstrate the feasibility of embryo transport by air for centers that do not have the in-house capabilities to perform genetic analysis. With successful pregnancies obtained through extended culture to Day 5, embryos requiring genetic analysis can be successfully transported by air, tested, and returned to the initial facility for embryo transfer without time restriction.